JP2016508808A - Frequency optimization in ultrasonic treatment - Google Patents

Abstract

In ultrasound therapy, the frequency of sonication can be optimized within a specific frequency range to maximize absorption or sound intensity at the target in a patient-specific manner. In one embodiment, a patient-specific frequency optimization method for targeted ultrasound therapy within a patient comprising: (a) at least one section of an ultrasound transducer and within a test range Sonicating the target for each of a plurality of ultrasonic frequencies and measuring a parameter correlated with the amount of ultrasonic energy absorbed at the target; and (b) for each of the at least one compartment Selecting a frequency corresponding to the measured parameter value among the frequencies within the test range for subsequent ultrasound therapy, wherein the measured parameter value itself is absorbed at the target. Corresponding to a maximum amount of ultrasonic energy.

Description

(Cross-reference to related applications)
This application claims priority and benefit of US Provisional Patent Application No. 61 / 773,394, filed Mar. 6, 2013, which is hereby incorporated by reference in its entirety.

(Technical field)
The present invention relates generally to focused ultrasound therapy, and more specifically to a system and method for optimizing ultrasound frequency for increased energy storage at a target.

(background)
Focused ultrasound (ie, acoustic waves having a frequency above about 20 kilohertz) can be used to image or therapeutically treat internal body tissue within a patient. For example, ultrasound may be used to remove a tumor, eliminating the need for patients to undergo invasive surgery. For this purpose, a piezoceramic transducer is placed outside the patient but in close proximity to the tissue to be excised (“target”). The transducer converts the electronic drive signal into mechanical vibrations, resulting in the emission of acoustic waves (hereinafter referred to as “sonication”). The transducer may be shaped so that the waves converge within the focusing band. Alternatively or additionally, the transducer may be formed from a plurality of individually driven transducer elements, each of whose phase (and optionally amplitude) may be controlled independently of each other. Can thus be set to provide constructive interference of individual acoustic waves within the focusing band. Such “phase array” transducers facilitate steering the focusing band to different locations by adjusting the relative phase between the transducers. Magnetic resonance images (MRI) may be utilized to visualize the focus and target to guide the ultrasound beam.

  FIG. 1 illustrates an exemplary MRI guided focused ultrasound system 100. System 100 includes a plurality of ultrasonic transducer elements 102 arranged as an array on the surface of housing 104. The array may comprise a single row or matrix of transducer elements 102 or, in general, any arrangement. The array may have a curved (eg, spherical or parabolic) shape, as shown, or may include one or more planes or otherwise shaped sections. Its dimensions may vary between a few millimeters and tens of centimeters, depending on the application. The transducer element 102 is a piezoceramic element or may be made from a piezoelectric composite or any other material capable of converting electrical energy into acoustic energy. In order to damp mechanical coupling between the elements 102, they may be mounted on the housing 104 using silicone rubber or any other suitable dampening material.

  The transducer element 102 is driven by the control facility 106 via a separate drive channel. In the case of n converter elements 102, the control facility 106 may include n control circuits, each comprising an amplifier and a phase delay circuit, each control circuit including one of the converter elements 102. To drive. The control facility may typically divide a radio frequency (RF) input signal in the range of 0.1 MHz to 4 MHz into n channels for n control circuits. In conventional systems, the control facility 106 collectively collects individual transducer elements 102 of the array at the same frequency but at different phases and amplitudes so as to produce a focused ultrasound beam at a desired location. Is configured to drive. The control facility 106 desirably provides computational functionality, which is implemented in software, hardware, firmware, hard wiring, or any combination thereof, and requires the phase and phase required for the desired focusing location. The amplitude may be calculated. These phase / amplitude calculations can be determined, for example, based on computed tomography (CT) or other images of the anatomical region of interest, aberrations resulting from ultrasound reflection or refraction at the tissue interface, or various acoustic parameters. Correction may be included to compensate for propagation in tissue having In general, the control facility 106 includes a frequency generator, a beamformer including an amplifier and a phase delay circuit, and a computer (eg, a general purpose computer) that performs calculations and communicates the phase and amplitude for each transducer 102 to the beamformer. Some detachable devices such as computers) may be included. Such a system is readily available or can be implemented without undue experimentation.

  System 100 further includes an MRI apparatus 108 in communication with control facility 106. Exemplary device 108 is illustrated in greater detail in FIG. The device 108 may include a cylindrical electromagnet 204 that generates a static magnetic field in the bore 206 of the electromagnet 204. During the medical procedure, the patient is placed on a movable support 208 inside the bore 206. A region of interest 210 within the patient (eg, the patient's head) may be positioned within an imaging region 212 where the magnetic field is substantially homogeneous. A radio frequency (RF) transmitter coil 214 surrounding the imaging region 212 emits RF pulses into the imaging region 212 and receives MR response signals emitted from the region of interest 210. The MR response signal is amplified, adjusted, digitized into raw data using an image processing system 216, and further converted into an array of image data by methods known to those skilled in the art. Based on the image data, a treatment area (eg, a tumor) is identified. Within the bore 206 of the MRI apparatus, in some embodiments, the ultrasound phase array 220 disposed within the imaging region 212 is then driven to focus the ultrasound into the treatment region. The MRI apparatus 108 facilitates visualizing the focal point 112 based on the effect on the tissue being sonicated. For example, any of a variety of MRI-based temperature measurement methods may be employed to observe the temperature increase resulting from ultrasound absorption in the focused region. Alternatively, MR-based acoustic radiation force imaging (ARFI) may be used to measure tissue displacement at the focal point. Such measurement of the focus can serve as feedback for driving the ultrasonic transducer array 220.

  The goal of focused ultrasound treatment generally is the amount of energy absorbed at the target while minimizing exposure of the healthy tissue surrounding the target and the tissue along the path between the transducer and the target to ultrasound. Is to maximize. The ultrasonic absorption in the tissue is a function of frequency determined by:

式中、Ｉ_０は、組織の中への進入点における超音波強度（Ｗ／ｃｍ^２で測定される）であり、Ｉは、距離ｚ（ｃｍで測定さされる）にわたる組織を通したビーム伝搬後の強度であり、ｆは、超音波の周波数（ＭＨｚで測定される）であり、αは、その周波数における吸収係数（ｃｍ^−１・ＭＨｚ^−１で測定される）である。積α・ｆが高いほど、標的領域内の吸収度は、大きくなるが、途中で吸収される超音波の割合もまた、より高くなり、したがって、標的領域に決して到達しない。本トレードオフは、組織深度ｚにおける１ｃｍの標的組織に沿って吸収される（すなわち、組織の距離ｚを通したビーム伝搬後の）超音波エネルギーの割合Ｅ_Ｔによって捉えられ得る。

Where I ₀ is the ultrasonic intensity at the point of entry into the tissue (measured in W / cm ² ) and I is the beam propagation through the tissue over a distance z (measured in cm). It is the latter intensity, f is the frequency of the ultrasonic wave (measured in MHz), and α is the absorption coefficient at that frequency (measured in cm ⁻¹ · MHz ⁻¹ ). The higher the product α · f, the greater the absorbance in the target area, but the higher the proportion of ultrasound absorbed along the way, so it never reaches the target area. This trade-off is absorbed along the 1cm of the target tissue in tissue depth z (i.e., after the beam propagation through the distance z of the tissue) may be captured by the percentage E _T of ultrasonic energy.

従来の超音波処置手技では、超音波周波数は、Ｅ_Ｔを最大限にするために、前述の関係に基づいて選択される。しかしながら、本アプローチは、反射、屈折、および散乱等の、焦点におけるエネルギー蓄積に影響を及ぼす他の超音波−組織相互作用の影響を考慮することができない。いくつかの状況では、そのような相互作用は、実質的である。例えば、超音波を脳の中に集束させるとき、ビームは、図３に図示されるように、皮質層から、および皮質層間で複数の反射を被り得る。故に、標的におけるエネルギー蓄積を改善するために周波数選択を精緻化する能力は、超音波処置の性能および安全性を改善する。

In the conventional ultrasonic treatment procedure, ultrasonic frequencies, in order to maximize E _T, is selected on the basis of the above-mentioned relationship. However, this approach cannot take into account the effects of other ultrasound-tissue interactions that affect energy accumulation at the focal point, such as reflection, refraction, and scattering. In some situations, such interaction is substantial. For example, when focusing ultrasound into the brain, the beam may experience multiple reflections from and between cortical layers, as illustrated in FIG. Hence, the ability to refine frequency selection to improve energy storage at the target improves the performance and safety of ultrasound treatment.

(Overview)
The present invention provides a focused ultrasound treatment method involving determining an optimum frequency within a specific frequency range, i.e., one that maximizes absorption or acoustic intensity at the target, and for implementing such a method. About the system. (The terms “optimized”, “optimized”, “maximum”, “maximized”, etc. as used herein generally represent a substantial improvement over the prior art (eg, greater than 10%, 20% Is not necessarily meant to achieve the best theoretically possible frequency, energy absorption, etc. Rather, optimizing the frequency or maximizing the energy at the target , Which involves selecting the best frequency that is practically discriminable within the limits of the technology and method utilized.) The present invention allows the amount of ultrasound energy absorbed at the target site to vary in tissue interactions other than absorption. Based on the recognition that it is significantly affected by the mechanism, the present invention can be significantly improved by selecting an ultrasonic frequency that deviates from the absorption-based frequency calculated conventionally. That.

  Thus, embodiments of the present invention consider multiple ultrasound-tissue interactions when selecting a treatment frequency. In principle, this can be accomplished computationally, for example, using finite element methods to simulate the interaction of the ultrasound beam and patient tissue at various frequencies. The simulation may be based on a detailed tissue model, such as obtained by computed tomography or ultrashort echo time (TE) MRI. The model generally includes multiple tissue types or layers (eg, for ultrasound focused into the skull, cortical bone layers, bone marrow, and soft brain tissue) and characterizes its individual material properties. However, the optimal frequency can often not be adequately captured using current tissue imaging and modeling techniques, or is computationally expensive to be impractical, despite similar target sites. It has been observed that in any one manner, it varies significantly from person to person. Thus, in a preferred embodiment, the optimal frequency is determined for each patient, both experimentally and individually. This is the ultrasound absorption (or quantity that represents it) at the target at some frequency within the defined range (generally low enough energy level to not cause any damage to the tissue) prior to treatment. And measuring the optimal frequency based on the measurement. The method implicitly considers all (known or unknown) contributors to the amount of ultrasonic energy absorbed at the target. Alternatively, if a particular mechanism such as reflection is found to affect the attenuation of the ultrasound between the transducer and the target, the effect of that mechanism is quantified experimentally and the frequency It may be selected to minimize. For example, when focusing ultrasound into the brain, the beam can experience multiple reflections from and between cortical layers. In this scenario, one way to optimize the frequency is to measure the total skull reflectivity (sum of contributions from all reflected beams) and select the frequency at which the reflected beam is minimized That is.

  Thus, in one embodiment, the present invention relates to a patient specific frequency optimization method for targeted ultrasound therapy within a patient. The method sonicates the target and, for each of a plurality of ultrasonic frequencies within the test range, parameters associated with the amount of ultrasonic energy absorbed into the target (eg, using temperature measurements) (eg, Power, energy, intensity, acoustic force, tissue displacement, and temperature). In some embodiments, the transducer includes a plurality of compartments (e.g., may be defined based at least in part on the patient's anatomy), and the parameters are measured for each test frequency and compartment. The Of the frequencies within the test range, the frequency corresponding to the value of the measured parameter that itself corresponds to the maximum amount of ultrasonic energy absorbed in the target is selected (for the entire transducer or for each compartment). To). In some embodiments, the plurality of frequencies within the test range are dynamically defined based at least in part on the value of a parameter measured with respect to previously tested frequencies. Following frequency selection, the transducer (or transducer section) may be driven at the selected frequency (or frequencies) and treatment energy level, thereby sonicating the target. The treatment energy level typically exceeds the sonication energy level applied during the test. In a multi-compartment embodiment, the compartments may be driven sequentially (eg, periodically) or simultaneously, each at its individually selected frequency.

  A further aspect is directed to a system for selecting a patient specific frequency for targeted ultrasound therapy within a patient. The system includes an ultrasonic transducer, an associated controller capable of driving the transducer at any frequency within a frequency test range to sonicate the target, and ultrasonic energy absorbed in the target. And a measurement facility (eg, an MRI apparatus) for measuring a parameter correlated with the quantity. The system further includes (i) sequentially driving one or more sections of the transducer for each of a plurality of frequencies within the test range to sonicate the target to the ultrasonic transducer controller. (Iii) causing the measurement facility to measure a parameter correlated to the amount of ultrasonic energy absorbed in the target for each of the frequencies; and (iii) for each of the compartments For subsequent focused ultrasound therapy, to select the frequency within the test range that corresponds to the value of the measured parameter that itself corresponds to the maximum amount of ultrasonic energy absorbed into the target Have computing facilities. In embodiments in which the ultrasound transducer has multiple compartments, the controller may be configured to cause the ultrasound transducer to drive the compartments together at their respective selected frequencies during ultrasound therapy. Good. Alternatively, the compartments may be driven continuously, for example periodically.

  Yet another aspect is to define a plurality of compartments in the ultrasound transducer array and to sonicate the target separately for each of the compartments at each of the plurality of frequencies within the test frequency range. A patient-specific frequency optimization method for targeted ultrasound therapy is provided that involves continuously driving the compartments. For each sonication, parameters (eg, power, energy, intensity, acoustic force, tissue displacement, and / or temperature) correlated with the amount of ultrasonic energy absorbed into the target are measured at each frequency ( For example, using temperature measurement or acoustic radiation force imaging). The parameter values measured for multiple compartments may be combined for each of multiple frequencies with a total parameter value that is correlated with the total amount of ultrasonic energy absorbed in the target. Of the plurality of frequencies, the frequency corresponding to the value of the measured total parameter that itself corresponds to the maximum total amount of ultrasonic energy absorbed into the target is then selected for subsequent therapy.

  In a further aspect, a system for selecting a patient specific frequency for targeted ultrasound therapy within a patient is provided. The system includes an ultrasonic transducer comprising a plurality of compartments and a controller capable of driving and associated with each of the transducer compartments at any of a plurality of frequencies within a frequency range to sonicate the target. A measurement facility (eg, an MRI apparatus) for measuring a parameter (eg, tissue displacement, etc.) correlated with the amount of ultrasonic energy absorbed into the target. Further, the system includes (i) causing the ultrasonic transducer controller to drive each of the compartments separately and sequentially for each of a plurality of frequencies within the test range to sonicate the target; ii) having the measurement facility measure a parameter correlated to the amount of ultrasonic energy absorbed in the target for each of the frequencies; and (iii) a plurality of compartments for each of the plurality of frequencies. Combining the measured parameter value with respect to the total parameter value correlated with the total amount of ultrasonic energy absorbed in the target, and (iv) of the multiple frequencies within the target for subsequent focused ultrasound therapy Including a computing facility for selecting the optimum frequency corresponding to the value of the measured total parameter, which itself corresponds to the maximum total amount of ultrasonic energy absorbed in. The controller may be configured to cause the ultrasound transducer to drive the compartments together at the optimal frequency selected during ultrasound therapy.

The foregoing and following detailed description will be more readily understood when considered in conjunction with the drawings.
FIG. 1 schematically illustrates an MRI guided focused ultrasound system, according to various embodiments. FIG. 2 illustrates an MRI system according to various embodiments. FIG. 3 illustrates ultrasound reflection by a tissue boundary located between the transducer and the treatment target in a brain treatment scenario. FIG. 4 is a flowchart illustrating a method for optimizing a sonication frequency according to various embodiments. 5A and 5B are graphs of energy absorption empirically determined from frequencies for an exemplary treatment scenario and their predicted dependence. 5A and 5B are graphs of energy absorption empirically determined from frequencies for an exemplary treatment scenario and their predicted dependence. FIG. 6 illustrates the segmentation of an ultrasound transducer for brain treatment, according to one embodiment. FIG. 7 is a flowchart illustrating a method for separately optimizing the sonication frequency of multiple transducer sections, according to various embodiments. FIG. 8 is a block diagram illustrating a system for optimizing sonication frequencies according to various embodiments.

(Detailed explanation)
In various embodiments, the present invention provides a method for optimizing the frequency of sonication in a focused ultrasound procedure for a particular patient. An exemplary method is illustrated in FIG. After the treatment configuration is set and the patient is placed in or against the ultrasound transducer and imaging device 108 (eg, as depicted in FIG. 2), images of relevant tissue regions are acquired and processed, Targets therein may be identified (step 400). The relative phase and / or amplitude setting of the ultrasonic transducer element 102 that provides beam focusing to the target is then converted into the relative position of the transducer and target and any a priori knowledge and / or image derivation information about the intervening tissue. Based on this, a calculation may be made (step 402). The phase and / or amplitude settings are experimentally refined one or more times before, after, and / or during the frequency optimization process based on observation of the focus quality and / or focus location on the target. (Step 404). Methods for computational and experimental phase / amplitude determination and adjustment are well known to those skilled in the art. The transducer is then driven according to the determined phase and amplitude settings to sonicate the target.

  In order to optimize the frequency of the ultrasound, the target is sonicated continuously at different “test frequencies” within the “test range” of the frequency, and for each frequency tested, a parameter indicating the energy absorption within the target. Is measured. The test range may span the full range of frequencies suitable for ultrasound treatment (eg, 0.1 MHz to 4 MHz in various embodiments), but typically in a much smaller sub-range. Among them, the optimal frequency is expected. Such subranges may be determined, for example, based on calculated estimates of optimal frequencies, simulation results, or experimental data obtained for the same organ or tissue in another patient. The frequencies to be tested may be distributed uniformly or non-uniformly over the test range. In various embodiments, the density of the test frequency increases as it approaches the estimated optimal frequency. The test range and test frequency therein may be predetermined or may be adjusted dynamically during the optimization process. For example, in one embodiment, the test is initially performed over a large test range (e.g., 600-750 kHz) with a large frequency interval (e.g., by 20 kHz) to produce a sub-range of frequencies that provides high energy absorption at the target. Once determined, the optimal frequency is then determined within the subrange by testing at smaller intervals (eg, 10 kHz or 5 kHz each). In another embodiment, the test is performed on a predetermined subset of potential test frequencies, and each actual test frequency is selected from a set of potential test frequencies based on the results of previous tests.

  Thus, frequency optimization involves iteratively setting the test frequency (step 406), sonicating the target at the selected frequency (step 408), eg, temperature within the target resulting from absorbed energy. MRI thermometry to measure increase, MR-ARFI to measure tissue displacement resulting from acoustic pressure at the target, ultrasonic detection to measure the intensity of reflected (ie, unabsorbed) ultrasound, or In general, quantitatively assess the resulting energy absorption at the target using any experimental technique for measuring a parameter that correlates with energy absorption at the target in a known and predictable manner (step 410). Accompanied by. A maximum value (eg, for temperature or pressure) or a minimum value (eg, for reflection) of the parameter being measured is then determined to identify the test frequency at which energy absorption at the target is maximized (step 412). Following frequency optimization, the phase and / or amplitude settings of the phase array transducer may be adjusted to optimize the focus for the selected frequency. Treatment may then begin at the optimal frequency and phase / amplitude setting (step 414).

The utility of frequency optimization according to this specification is that energy absorption varies significantly and often non-monotonically with frequency, and the optimal frequency for a particular patient is typically unpredictable. Derived from the fact that For example, FIG. 5A illustrates ultrasound peak intensities measured at several frequencies from 600 kHz to 760 kHz for an in vitro skull with a hydrophone placed inside the skull. As shown, the peak intensity achieved at 600 kHz is about 50% higher than that at 720 kHz, and the peak intensity at 740 kHz is more than 30% higher than that at 720 kHz. Such large intensity fluctuations over the short frequency range are surprising when compared to intensity fluctuations with frequencies resulting from absorption alone, as modeled using equation (2). (FIG. 5B uses equation (2) to absorb, for example, at a 1 cm target located 6 cm inside soft tissue with an absorption coefficient of α = 0.06 Napiers / cm / MHz (approximate for brain tissue). Shows the percentage of energy Ε _{T. As} can be seen, the absorbed energy fluctuates smoothly as a function of the ultrasonic frequency and is the experimentally found minimum at 720 Hz reflected in FIG. Similar measurements on different skulls can also reveal high fluctuations in peak intensity, but generally involve different frequency dependencies (e.g., intensity is minimized or maximized). Different frequency).

  In certain treatment scenarios, ultrasonic waves propagating from different directions toward the target may encounter highly variable anatomy such as different thickness tissue layers and different acoustic impedances. For example, during a transcranial ultrasound procedure, acoustic beams originating from different directions may encounter variability in absorption coefficients within different thicknesses of cortical skull, different thicknesses of bone marrow, etc., as well as soft tissue. In various other clinical scenarios, some of the soft tissue may have a much higher calcification content than expected and thus have a much higher attenuation in the near field. In these cases, the overall energy storage at the target optimizes the frequency separately for different regions or sections of the transducer array, and then simultaneously or sequentially, not at the single frequency of the entire transducer, It may be improved by driving the transducer at multiple frequencies for different sections.

  The compartmentalization of the transducer array (or group of transducer elements) for such compartment-based frequency optimization is the similarity of the relevant paths through the anatomy for the different transducer elements, each transducer It may be based on the ability to generate a sufficiently high quality focus using the compartment (eg, depending on the total number of elements in the compartment) and the final combined therapeutic effect provided by all transducer compartments. For example, if the array is divided into too many, too small sections (in an attempt to maximize the benefits of frequency optimization), the individual sections no longer have effective focusing capability and the beam is scattered Therefore, there may be a case where a sufficiently clear focus cannot be generated. FIG. 6 illustrates a preferred compartmentalization of a generally hemispherical transducer used for brain tumor treatment. In the depicted embodiment, the transducer array is divided into seven sections of a central “cap” and six similarly sized perimeter “tiles”. In general, the transducer may have more or fewer compartments. A typical transducer split includes 3 to 15 sections.

  FIG. 7 illustrates a method for optimizing the frequency of a multi-compartment transducer. After targets within the patient are identified in step 400 (eg, based on the image), transducer sections are defined (step 700), and the focus of each section generates a high quality focus at the target location. May be optimized separately by setting and adjusting the relative phase and / or amplitude between the transducer elements of that compartment (steps 402, 404), and in the manner described above, at the target A frequency dependent raw within the test range of energy absorption is determined (steps 406, 408, 410). In some embodiments, the optimal frequency (ie, the frequency that maximizes energy absorption at the target) is identified separately for each partition (step 412). To treat the target, the separately optimized transducer section may then be driven continuously or together for each of its own optimal frequencies (step 702). For example, the compartments may prevent ultrasonic waves from compartments driven at different frequencies from destructively interfering, and at the same time, the energy stored in the target will not be significantly lost during each sonication cycle. May be driven separately and periodically. In an alternative embodiment, a single frequency that maximizes the overall absorption of ultrasonic energy received from the various compartments is inferred from the individual measured frequency dependences in the manner further described below ( Step 704), the various compartments are tested separately, but all are driven at that same overall optimal frequency during the procedure (step 706). Driving the compartments at a single common frequency may advantageously provide a smaller focus with higher peak intensity to ensure constructive interference of ultrasound from different compartments.

  Various techniques, directly or indirectly, measure energy absorption in the target via the associated physical quantity, and then maximize the amount of energy absorbed through selection of the optimal frequency Can be used for. One approach is to monitor the temperature at the target, which proportionally increases the amount of energy absorbed. The temperature measurement method may be based on MRI, for example, and may utilize a system such as that depicted in FIG. 2 in conjunction with suitable image processing software. Among the various methods available for MR temperature measurement, the proton resonance frequency (PRF) shift method has its excellent linearity to temperature changes, quasi-independence from tissue type, and high spatial and temporal resolution. This is often the method chosen by acquiring a temperature map with The PRF shift method utilizes a phenomenon in which the MR resonance frequency of protons in water molecules changes linearly with temperature. Since the frequency change with temperature is only -0.01 ppm / ° C for bulk water and as small as about -0.0096 to -0.013 ppm / ° C in tissue, the PRF shift is typically phase Detected using a sensitive imaging method, imaging is performed twice, first acquiring a baseline PRF phase image before the temperature change, and then acquiring a second phase image after the temperature change; Thereby, a slight phase change proportional to the temperature change is captured. A map of temperature changes is then made between the baseline image and the treatment image for each pixel, taking into account imaging parameters such as the strength of the static magnetic field and the echo time (TE) (eg of a gradient entry call echo). It may be calculated from the MR image by determining the phase difference and converting the phase difference into a temperature difference based on the PRF temperature dependence. Various alternative or advanced methods may be used to compensate for patient movement, magnetic field drift, and other factors that affect the accuracy of PRF-based temperature measurements. Suitable methods known to those skilled in the art include, for example, multi-baseline and no reference temperature measurements.

  Using a PRF-based or any other suitable temperature measurement method, the optimal ultrasonic frequency within the specified range is the same power and duration (or more generally total transmitted energy). While continuously driving the transducer at several different frequencies (eg, a defined frequency interval within a selected range) to focus the ultrasound to a specific patient target site, For each treatment, it can be determined by measuring the temperature increase at the target. This is done prior to treatment. Thus, to avoid tissue damage, the ultrasound transducer is driven at a much lower power than during subsequent procedures (but high enough to obtain a meaningful signal-to-noise ratio). Furthermore, each temperature increase is preferably measured against a similar baseline temperature to ensure comparability of measurements for different frequencies. This will allow sufficient time following each sonication to cool the tissue to a temperature approximately equal to the baseline temperature, limiting the effect on the tissue due to temperature changes (eg, clinically). (Not significant) can be accomplished by using sufficiently low energy. When the temperature increase is measured at various discrete frequencies within the range of interest, the frequency at which the temperature increase is maximum is selected to operate the transducer during the subsequent procedure. In embodiments where the frequency is optimized separately for multiple transducer sections, the procedure is performed for each section. During the procedure, the various compartments may be driven together or alternately (eg, circulating through the compartments) for their respective optimal frequencies.

  Another quantity that is usefully related to the absorption of ultrasonic energy in the tissue is the temporary locality of the tissue due to the acoustic radiation pressure, which is highest at the focal point (where the wave converges and the highest intensity is achieved). Displacement. The ultrasonic pressure generates a displacement field that directly reflects the acoustic field. The displacement field can be visualized by applying a magnetic field gradient that is sensitive to transient motion or displacement to the imaging region by means of a gradient coil, using techniques such as MR-ARFI, It is part of a standard MRI apparatus (such as apparatus 108 depicted in FIG. 2) and is typically located near the cylindrical electromagnet 204. When an ultrasonic pulse is applied in the presence of such a gradient, the resulting displacement is encoded directly into the phase of the MR response signal. For example, the gradient coil and transducer may be configured so that the ultrasound pulse pushes the material near the focal point toward the region of the magnetic field with higher field strength. In response to the resulting magnetic field change, the phase of the MR response signal changes proportionally, thereby encoding the displacement caused by the ultrasonic radiation pressure into the signal. Further details regarding MR-ARFI are provided in US patent application Ser. No. 12 / 769,059 filed Apr. 28, 2010, the entire disclosure of which is hereby incorporated by reference.

  For a given transducer array, the tissue displacement measured using MR-ARFI is directly proportional to the ultrasound intensity. Advantageously, the energy required to obtain a good displacement signal is very small compared to typical therapeutic energy (and for a very short period of time, eg about 20 ms, Achieved by processing), making ARFI a good candidate for pre-treatment optimization. However, the displacement forces generated by ultrasonic waves originating from different directions are partially offset from each other. Thus, when using MR-ARFI to tune the frequency for maximum energy absorption at the focus, the frequency will eventually be even when a single frequency is selected to drive the entire transducer array. Preferably, it is optimized separately for multiple transducer sections (each not covering a very large solid angle). The overall optimum frequency is derived from the optimum frequencies for the individual partitions by combining them in a suitable manner (as described below). (In contrast to radiant power, thermal energy due to different compartments and ultrasonic directions accumulates without cancellation. Therefore, when using temperature measurement for frequency optimization, the procedure is generally applied to the transducer. May be performed on the array).

Since the purpose of the various embodiments is to find the optimal treatment frequency for a particular patient by a procedure that is part of the treatment flow, the procedure is preferably short, eg, about a few minutes. . This can be achieved using ARFI if the number of transducer sections and the number of discrete frequencies to be tested are not very large. For example, to determine the best frequency for a curved (eg, hemispherical) ultrasonic transducer used in brain tumor treatment, the transducer is, for example, seven compartments (as illustrated in FIG. And 6 tiles) or even only 4 compartments (cap and 3 tiles). The compartments may be defined based on general criteria such as the solid angle they cover, or based on more detailed criteria relating to the anatomy of a particular patient, for example. Tissue displacement may be measured for each compartment at about 10 different frequencies or less, for example, at 9 frequencies (as shown in FIG. 5A) at 20 kHz intervals in the range of 600 kHz to 760 kHz. The number of partitions using Ns, when the number of discrete frequencies with N _f, measurement of total Ns · N _f, is required.

  For each compartment, a single scan covering all frequencies may be performed in the lateral plane (or multiple, eg, 3 parallel planes) that pass through the focal point of that compartment (all compartments work together). May be slightly displaced from the theoretical focus location, sometimes achieved). MR scans are synchronized with ultrasound pulses that generate tissue displacement. In some cases, the relative phase between elements of the transducer section is corrected based on, for example, CT images or other a priori knowledge, for example, to compensate for bone variability. Using the state-of-the-art focused ultrasound / MR-ARFI system, the MR scan, in one embodiment, is approximately 20 seconds ready (eg, PSD download and pre-scan to optimize scan parameters), ARFI Requires about 3 seconds to obtain a reference image for and about 3 seconds per frequency to generate a focus and measure the resulting tissue displacement (9 frequencies corresponds to 27 seconds) . The total time to determine the optimal frequency for a section is therefore less than 1 minute. Efficiency gain can result from common overhead and common reference used for all frequencies. (The calculation time for processing the data is negligible compared to the time for taking the measurements.) The total time required for the entire transducer with 7 sections is the example given above. Then it is about 7 minutes.

Tissue displacement measured for all sections and frequency, N _f × N _s array D _ij in may be stored in the row i corresponds to the frequency f _i, column j corresponds to the converter section j . If the compartments are driven at different frequencies, the optimal frequency is determined for each column D _i1 , D _i2,. . . _Determined by finding the largest entry i in D _iNs and selecting the frequency f _i for the corresponding partition.

If a single optimal frequency is determined for the entire transducer, a new value D _{combined — i} , where entries across the columns in each line i (ie, for each frequency f _i ) capture the contribution of all partitions. To be combined. If different compartments are driven at different total powers (eg, proportional to their individual areas) during measurement, the individual measured displacements D _ij are typically first normalized as appropriate. Is done. The _combined displacement D _{combined_i} is then calculated in one of several ways that yields a value that is clearly correlated to the combined treatment effect of all compartments (some but not all of which Or has a physical interpretation). For example, in some embodiments, the combined displacement values are calculated by summing the square roots of the individual displacements, squaring the result, and determining a value proportional to the total peak intensity at the focus, as follows: (Assuming that the relative phase between subfocals generated using different sections, which can be guaranteed by computed tomography based correction, is correct).

他の実施形態では、組み合わせられた変位値は、単に、個々の変位の絶対値の和であり、集束領域内に印加された総電力と比例する。

In other embodiments, the combined displacement value is simply the sum of the absolute values of the individual displacements and is proportional to the total power applied in the focusing region.

さらに別の実施形態では、変位ベクトルＤ_ｉのＬ_２−ノルムは、以下のように計算される。

In yet another embodiment, the L ₂ -norm of the displacement vector D _i is calculated as follows:

組み合わせられた変位が計算される様式は、例えば、最適化されるべきパラメータ（例えば、ピーク圧力または総電力）に依存し得る。前述の３つの実施形態は、単に、例である。同様に、他のノルム（または、ノルムではない変数）が、区画の組み合わせられた寄与と相関する限り、使用されてもよい。組み合わせられたベクトルＤ_{ｃｏｍｂｉｎｅｄ}の要素は、種々の周波数における総熱蓄積に比例する（または、相関される）。したがって、変換器の最適周波数は、最大組み合わせ変位が生じる周波数を識別することによって、決定されることができる。当然ながら、複数の区画のために別個に行われた測定から全体的最適周波数を決定することは、組織変位の測定に限定されない。組織変位以外のパラメータが、標的におけるエネルギー配置のインジケータとして使用される実施形態では、本パラメータの測定も同様に、全体的最適値を見つけるために、区画を横断して組み合わせられることができる。

The manner in which the combined displacement is calculated can depend, for example, on the parameter to be optimized (eg, peak pressure or total power). The three embodiments described above are merely examples. Similarly, other norms (or non-norm variables) may be used as long as they correlate with the combined contribution of the compartments. The elements of the _combined vector D _combined are proportional (or correlated) to the total heat accumulation at various frequencies. Thus, the optimal frequency of the transducer can be determined by identifying the frequency at which the maximum combined displacement occurs. Of course, determining the overall optimum frequency from measurements made separately for multiple compartments is not limited to measuring tissue displacement. In embodiments where parameters other than tissue displacement are used as indicators of energy placement at the target, the measurement of this parameter can also be combined across compartments to find an overall optimum.

  The approach described above is a suitable computing facility that works in conjunction with one or more ultrasound transducers and devices (eg, MRI devices) to measure the energy stored in the focus or another parameter indicative thereof. Can be implemented using. The computing equipment may be implemented in hardware (eg, circuitry), software, firmware, or any suitable combination thereof, in the ultrasound controller (eg, control equipment 106 in FIG. 1) and / or in the target. It may be provided as a separate device that is integrated with or in communication with an imaging device or other device for measuring energy storage (eg, image processing system 216 of FIG. 2).

  In some embodiments, the computing facility may be implemented using a suitably programmed general purpose computer. FIG. 8 illustrates an exemplary embodiment. Computer 800 includes one or more processors 802 (eg, CPU) and associated system memory 804 (eg, RAM, ROM, and / or flash memory) and user input / output devices (screen 806 and keyboard, mouse, etc. 808) and typically one or more (typically non-volatile) storage media 810 (eg, hard disk, CCD, DVD, USB memory key, etc.) and associated drive. . The various components may communicate with each other and with external devices (such as ultrasound transducers and / or imaging devices) via one or more system buses 812.

  The system memory 804 includes instructions conceptually illustrated as a group of modules that control the operation of the processor 802 and its interaction with other hardware components. The operating system 820 commands the execution of low-level basic system functions such as memory allocation, file management, and peripheral device operations. At a higher level, one or more service applications provide the computational functionality required for frequency optimization in accordance with this specification. For example, as shown, the system analyzes an image from an MRI (or other imaging) device, identifies the target therein, visualizes the focus, and ensures that it matches the target. An image processing module 822 that allows for calculating the relative phase and amplitude of the transducer elements based on the target location, and for controlling ultrasonic transducer operation during both frequency optimization and treatment Transducer control module 824 and functionality to obtain data regarding the frequency dependence of energy absorption at the target and to select an optimal frequency (or multiple individual optimal frequencies for various transducer sections) based thereon And a frequency optimization module 826 that provides: More specifically, the test sub-module 828 determines and / or receives inputs that define the test range and test frequency and causes the transducer control module 824 to continuously sonicate the target at these frequencies. And, for each sonication, receive and / or analyze images or other data that allow quantification of the energy absorbed at the target. Based on this information, the frequency selection module 830 determines the frequency or multiple frequencies (for multiple individually optimized sections) that maximize energy absorption at the target, or traverses the transducer sections. Measurements of absorption related parameters may be combined (eg, by calculating one of the aforementioned norms) to find a frequency that maximizes the overall amount of energy absorbed at the target.

  Of course, the depicted organization of computational functionality into various modules is just one possible way of grouping software functions. As those skilled in the art will readily appreciate, fewer, more, or different modules may be used to facilitate frequency optimization in accordance with this specification. However, the software grouped and organized is programmed in any of a variety of suitable programming languages including, but not limited to, C, C ++, Fortran, Pascal, Basic, Python, assembly language, or combinations thereof. May be. In addition, as an alternative to software instructions executed by a general purpose processor, some or all of the functionality is provided as programmable or wired custom circuits, including, for example, digital signal processors, programmable gate arrays, application specific integrated circuits, etc. May be.

  The terms and expressions employed herein are used for descriptive terms and expressions, not limitations, and the use of such terms and expressions may include any equivalents of the features illustrated and described or portions thereof. There is no intention to exclude. In addition, while certain embodiments of the invention have been described, it is to be understood that other embodiments incorporating the concepts disclosed herein may be used without departing from the spirit and scope of the invention. Will be apparent to those skilled in the art. For example, instead of MR-based temperature measurement or ARFI, any non-invasive imaging technique that can measure the (physical or therapeutic) effect of an acoustic beam at the focal point is generally in accordance with the present specification with an optimal frequency (or , Multiple optimal frequencies for different partitions) may be used. Accordingly, the described embodiments are to be considered in all respects only as illustrative and not restrictive.

Claims (19)

A patient-specific frequency optimization method for targeted ultrasound therapy within a patient, the method comprising:
(A) the amount of ultrasonic energy that is sonicated and absorbed at the target for at least one section of the ultrasonic transducer and for each of a plurality of ultrasonic frequencies within a test range; Measuring parameters correlated with
(B) for each of the at least one section, selecting a frequency corresponding to the value of the measured parameter among the frequencies within the test range for subsequent ultrasound therapy; The value of the measured parameter itself corresponds to the maximum amount of ultrasonic energy absorbed at the target.   Following the frequency selection in step (b), driving the at least one section to the selected frequency and therapeutic energy level, thereby sonicating the target, the therapeutic energy level The method of claim 1, further comprising: exceeding the energy level of the sonication applied in step (a).   The method of claim 1, further comprising defining a plurality of compartments in the ultrasound transducer based at least in part on the anatomy of the patient.   Step (a) and step (b) are performed for each of the compartments, and the method further comprises driving the compartments together at their respective selected frequencies during ultrasound therapy. 4. The method of claim 3, comprising.   The method of claim 1, wherein a plurality of frequencies within the test range are dynamically defined based at least in part on a value of a parameter measured with respect to previously tested frequencies.   The method of claim 1, wherein the parameter is selected from the group consisting of power, energy, intensity, acoustic force, tissue displacement, and temperature.   The method of claim 1, wherein the parameter is measured using a temperature measurement. A system for selecting a patient specific frequency for ultrasound therapy of a target within a patient, the system comprising:
An ultrasonic transducer and an associated controller capable of driving the transducer at any frequency within a frequency test range to sonicate the target;
A measurement facility for measuring a parameter correlated with the amount of ultrasonic energy absorbed at the target;
(I) causing the ultrasonic transducer controller to continuously drive at least one section of the transducer at each of a plurality of frequencies within the test range to sonicate the target; ii) having the measurement facility measure a parameter correlated to the amount of ultrasonic energy absorbed at the target for each of the frequencies; and (iii) for each of the at least one compartment. Selecting a frequency corresponding to the value of the measured parameter among the frequencies within the test range for subsequent focused ultrasound therapy, wherein the measured parameter value itself is And a computing facility for corresponding to the maximum amount of ultrasonic energy absorbed at the target.   The system of claim 8, wherein the measurement facility comprises a magnetic resonance imaging device.   The system of claim 8, wherein the ultrasonic transducer comprises a plurality of compartments.   The system of claim 10, wherein the controller is configured to cause the ultrasound transducer to drive the compartments together at their respective selected frequencies during ultrasound therapy. A patient-specific frequency optimization method for targeted ultrasound therapy within a patient, the method comprising:
Defining a plurality of compartments in the ultrasonic transducer array;
Separately driving the compartment for each of a plurality of frequencies within a test frequency range to sonicate the target separately to the compartment;
Measuring a parameter correlated with the amount of ultrasonic energy absorbed at the target for each of the frequencies;
For each of the plurality of frequencies, combining the values of the parameters measured for the plurality of compartments into a total parameter value correlated with a total amount of ultrasonic energy absorbed at the target;
For the subsequent focused ultrasound therapy, selecting a frequency corresponding to the measured total parameter value among the plurality of frequencies, wherein the measured total parameter value itself is the target Corresponding to the maximum total amount of ultrasonic energy absorbed in the method.   The method of claim 12, wherein the parameter is selected from the group consisting of power, energy, intensity, acoustic force, tissue displacement, or temperature.   The method of claim 12, wherein the parameter is measured using a temperature measurement.   The method of claim 12, wherein the parameter is measured using acoustic radiation force imaging. A system for selecting a patient specific frequency for ultrasound therapy of a target within a patient, the system comprising:
An ultrasonic transducer comprising a plurality of compartments and an associated controller capable of driving each of the transducer compartments at any of a plurality of frequencies within a range of frequencies to sonicate the target;
A measurement facility for measuring a parameter correlated with the amount of ultrasonic energy absorbed at the target;
(I) causing the ultrasonic transducer controller to drive each of the compartments separately and continuously at each of a plurality of frequencies within a test range to sonicate the target; Causing a measurement facility to measure, for each of the frequencies, a parameter correlated to the amount of ultrasonic energy absorbed at the target; and (iii) for each of the plurality of frequencies Combining the values of the parameters measured for a compartment into a total parameter value correlated with the total amount of ultrasonic energy absorbed at the target; (iv) for the subsequent focused ultrasound therapy, Of the measured total parameter values, the optimum frequency corresponding to the measured total parameter value is selected, and the measured total parameter value itself is: It is absorbed in the serial target and a calculation facility for the correspond to the maximum amount of ultrasonic energy, the system.   The system of claim 16, wherein the measurement facility comprises a magnetic resonance imaging device.   The system of claim 16, wherein the measured parameter is tissue displacement.   The system of claim 16, wherein the controller is configured to cause the ultrasound transducer to drive the compartments together at the selected optimal frequency during ultrasound therapy.

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